Einfluss von metabolisch wirksamen Hormonen auf die IL-6-induzierte Signaltransduktion
The cytokine interleukin (IL)-6 exerts pro- and anti-inflammatory properties and is a main inducer of the acute-phase response. It is involved in the pathogenesis of inflammatory diseases like for example rheumatoid arthritis or multiple sclerosis. Glucocorticoids are steroid hormones that are widely used in the therapy of inflammatory diseases because of their anti-inflammatory effects. Therefore, it is important to examine the interactions of IL-6 and glucocorticoids in more detail. It has been known since several years that glucocorticoids increase the IL-6-induced acute-phase gene expression in the liver. However, the underlying molecular mechanisms are still not completely understood. In this work it could be shown both in the human hepatoma cell line HepG2 and in primary murine hepatocytes that glucocorticoids interfere with the IL-6-induced expression of the SOCS3 feedback inhibitor, thereby leading to an upregulation of IL-6-induced gene expression. Impaired transactivation of the glucocorticoid receptor abolishes the effect of glucocorticoids on IL-6-induced signal transduction. In a second project the influence of glucagon, an antagonist of insulin in the body, on the IL-6-induced signal transduction was investigated in primary murine hepatocytes. It could be shown that glucagon inhibits the IL-6-induced phosphorylation of the MAP kinases ERK1/2 and the IL-6-induced ERK1/2-dependent gene expression by redundant action of PKA and Epac. Moreover, in microarray analyses new ERK1/2-dependent target genes of IL-6 could be identified. In sum, a new mechanism of both glucocorticoid and glucagon action, each with a broad effect on IL-6 signaling, could be revealed in this study.
info:eu-repo/classification/ddc/570, Entzündung, Interleukin 6, Glucagon, Signaltransduktion, Cytokine, Leber, Biowissenschaften, Biologie, Glucocorticoid, Akutphase-Reaktion, inflammation, interleukin-6, signal transduction
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